This study focuses on the longitudinal clinical, biochemical, and physiological evaluation and treatment of mania, depression, schizoaffective illness and related anxiety disorders and psychoses. In double-blind, placebo-controlled clinical trials we have found the temporal lobe-limbic anticonvulsant carbamazepine useful in the treatment of both phases of manic-depressive illness. Drugs such as piribedil, pimozide, and clonidine, which have effects at catecholamine receptors, also appear to have clinical and theoretically important effects in patients with affective illness. Neurotransmitter amine, endocrine, and peptide substances implicated in the regulation of mood and behavior are studied and measured in plasma and cerebrospinal fluid of patients and normal controls as an approach to brain function. Animal models, such as kindling and cocaine sensitization, are studied as they provide new approaches to the mechanisms underlying progressive development of behavioral pathology and suggest new treatment strategies such as carbamazepine for affective illness.